Journal Article

DZNE-2021-01591

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Meta-analyses identify DNA methylation associated with kidney function and damage.

Schlosser, P. ; Tin, A. ; Matias-Garcia, P. R. ; Thio, C. H. L. ; Joehanes, R. ; Liu, H. ; Weihs, A. ; Yu, Z. ; Hoppmann, A. ; Grundner-Culemann, F. ; Min, J. L. ; Adeyemo, A. A. ; Agyemang, C. ; Ärnlöv, J. ; Aziz, N. A.DZNE* ; Baccarelli, A. ; Bochud, M. ; Brenner, H. ; Breteler, M.DZNE* ; Carmeli, C. ; Chaker, L. ; Chambers, J. C. ; Cole, S. A. ; Coresh, J. ; Corre, T. ; Correa, A. ; Cox, S. R. ; de Klein, N. ; Delgado, G. E. ; Domingo-Relloso, A. ; Eckardt, K.-U. ; Ekici, A. B. ; Endlich, K. ; Evans, K. L. ; Floyd, J. S. ; Fornage, M. ; Franke, L. ; Fraszczyk, E. ; Gao, X. ; Gào, X. ; Ghanbari, M. ; Ghasemi, S. ; Gieger, C. ; Greenland, P. ; Grove, M. L. ; Harris, S. E. ; Hemani, G. ; Henneman, P. ; Herder, C. ; Horvath, S. ; Hou, L. ; Hurme, M. A. ; Hwang, S.-J. ; Jarvelin, M.-R. ; Kardia, S. L. R. ; Kasela, S. ; Kleber, M. E. ; Koenig, W. ; Kooner, J. S. ; Kramer, H. ; Kronenberg, F. ; Kühnel, B. ; Lehtimäki, T. ; Lind, L. ; Liu, D.DZNE* ; Liu, Y. ; Lloyd-Jones, D. M. ; Lohman, K. ; Lorkowski, S. ; Lu, A. T. ; Marioni, R. E. ; März, W. ; McCartney, D. L. ; Meeks, K. A. C. ; Milani, L. ; Mishra, P. P. ; Nauck, M. ; Navas-Acien, A. ; Nowak, C. ; Peters, A. ; Prokisch, H. ; Psaty, B. M. ; Raitakari, O. T. ; Ratliff, S. M. ; Reiner, A. P. ; Rosas, S. E. ; Schöttker, B. ; Schwartz, J. ; Sedaghat, S. ; Smith, J. A. ; Sotoodehnia, N. ; Stocker, H. R. ; Stringhini, S. ; Sundström, J. ; Swenson, B. R. ; Tellez-Plaza, M. ; van Meurs, J. B. J. ; van Vliet-Ostaptchouk, J. V. ; Venema, A. ; Verweij, N. ; Walker, R. M. ; Wielscher, M. ; Winkelmann, J. ; Wolffenbuttel, B. H. R. ; Zhao, W. ; Zheng, Y. ; Team, E. B. R. (Collaboration Author) ; Consortium, G. o. D. M. (Collaboration Author) ; Loh, M. ; Snieder, H. ; Levy, D. ; Waldenberger, M. ; Susztak, K. ; Köttgen, A. ; Teumer, A. ; Milani, L.

2021
Nature Publishing Group UK [London]

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Please use a persistent id in citations: doi:10.1038/s41467-021-27234-3

Abstract: Chronic kidney disease is a major public health burden. Elevated urinary albumin-to-creatinine ratio is a measure of kidney damage, and used to diagnose and stage chronic kidney disease. To extend the knowledge on regulatory mechanisms related to kidney function and disease, we conducted a blood-based epigenome-wide association study for estimated glomerular filtration rate (n = 33,605) and urinary albumin-to-creatinine ratio (n = 15,068) and detected 69 and seven CpG sites where DNA methylation was associated with the respective trait. The majority of these findings showed directionally consistent associations with the respective clinical outcomes chronic kidney disease and moderately increased albuminuria. Associations of DNA methylation with kidney function, such as CpGs at JAZF1, PELI1 and CHD2 were validated in kidney tissue. Methylation at PHRF1, LDB2, CSRNP1 and IRF5 indicated causal effects on kidney function. Enrichment analyses revealed pathways related to hemostasis and blood cell migration for estimated glomerular filtration rate, and immune cell activation and response for urinary albumin-to-creatinineratio-associated CpGs.

Keyword(s): Adult (MeSH) ; Aged (MeSH) ; CpG Islands (MeSH) ; DNA Methylation (MeSH) ; Female (MeSH) ; Glomerular Filtration Rate (MeSH) ; Humans (MeSH) ; Interferon Regulatory Factors: genetics (MeSH) ; Interferon Regulatory Factors: metabolism (MeSH) ; Kidney: metabolism (MeSH) ; Kidney: physiopathology (MeSH) ; Kidney Function Tests (MeSH) ; LIM Domain Proteins: genetics (MeSH) ; LIM Domain Proteins: metabolism (MeSH) ; Male (MeSH) ; Membrane Proteins: genetics (MeSH) ; Membrane Proteins: metabolism (MeSH) ; Middle Aged (MeSH) ; Renal Insufficiency, Chronic: genetics (MeSH) ; Renal Insufficiency, Chronic: metabolism (MeSH) ; Renal Insufficiency, Chronic: physiopathology (MeSH) ; Transcription Factors: genetics (MeSH) ; Transcription Factors: metabolism (MeSH)

Note: (CC BY)

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Contributing Institute(s):

1. Population & Clinical Neuroepidemiology (AG Aziz)
2. Population Health Sciences (AG Breteler 1)

Research Program(s):

1. 354 - Disease Prevention and Healthy Aging (POF4-354) (POF4-354)

Appears in the scientific report 2021

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